Professional Experience

Research Goal

The goal of my lab’s research program is to provide basic science information that will lead to the development of more effective vaccines and drugs against bacterial infections.

Current Research

Our research program focuses on the structure determination of integral membrane proteins. We perform X-ray crystallography and functional analysis of these proteins using biophysical, biochemical, and cell biological techniques. We study transporters embedded in the outer membranes of Gram-negative bacteria, which are surface accessible and therefore have the potential to be good vaccine and/or drug targets against infectious diseases. We also study the membrane associated or soluble protein partners that interact with outer membrane transporters to understand how these systems function in vivo. Current topics in the lab include (1) small molecule and protein import across the bacterial outer membrane, (2) protein secretion by pathogenic bacteria, and (3) protein import across mitochondrial outer membranes.

Applying Our Research

This work advances medical research and will directly benefit the public. We have already succeeded in identifying an alternative drug treatment to antibiotics that may result in reduced multi-drug resistance in bacterial pathogens. We have also spent several years developing novel vaccines against plague. The approaches we use can be similarly applied to other bacterial diseases.

Need for Further Study

Multidrug resistance arising from indiscriminate and widespread use of antibiotics is a growing health threat, and we need to develop much better strategies for treatment and prevention of bacterial infections.

Research in Plain Language

Proteins are essential to life. They play a role in all types of biological processes in all species of plants, animals, and bacteria. Our research determines how proteins function by analyzing their three-dimensional structure.

Specifically, we study proteins on the surface of bacteria that help them move, release substances, and stick together. These proteins either help bacteria survive or cause diseases. Because these proteins are found on the surface of bacteria, vaccines and drugs can get to them. Knowing the structure of these particular proteins may help researchers develop therapies that fight infectious bacteria cells without hurting a patient’s own cells.

My lab studies several distinct proteins. Some are common to many different kinds of bacteria and are required for their survival. Others are uniquely involved in the development of specific infections, including the bacteria that causes plague. Recently, we have also started to study proteins that may play a role in Alzheimer’s and Parkinson’s diseases.

Related Links

Research Images

Molecular Dynamics for TbpA

This movie shows the results of the molecular dynamics simulations that were designed to mimic interactions of Neisserial TbpA with the TonB system. The conformational changes within the plug domain were monitored and analyzed for the formation of a pore that potentially represents a pathway for iron transport.

Mechanism for Iron Import by Neisseria Movie A

This movie shows how Neisseria are able to extract iron from transferrin for transport across the outer membrane. While TbpB presumably dissociates from hTf once iron is released, the mechanism for dissociation of apo-hTf from TbpA is not known. (Long version with annotations)

Mechanism for Iron Import by Neisseria Movie B

This movie shows how Neisseria are able to extract iron from transferrin for transport across the outer membrane. While TbpB presumably dissociates from hTf once iron is released, the mechanism for dissociation of apo-hTf from TbpA is not known. (Short version without annotations)

Neisserial Iron Import Complex

Neisseria survive in the human host by utilizing surface receptors to pirate iron from human iron binding proteins. Based on our studies, we were able to describe what the Neisserial import complex looks like at the surface of the pathogen. Shown here is the iron transporter TbpA (purple, red glow indicates iron passage), the co-receptor TbpB (purple, top), the human iron binding protein transferrin (orange), periplasmic proteins FbpA (dark green), and TonB (light green).

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The National Institute of Diabetes and Digestive and Kidney Diseases
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